Evaluation of poly(lactic acid)/ and poly(lactic-co-glycolic acid)/ poly(ethylene adipate) copolymers for the preparation of paclitaxel loaded drug nanoparticles

Abstract

The present study evaluates the use of novel poly(lactic acid)/poly(ethylene adipate) (PLA-PEAd) and poly(lactic-co-glycolic acid)/poly(ethylene adipate) (PLGA-PEAd) copolymers for the preparation of paclitaxel (PTX) loaded nanoparticles (NPs). Specifically, four copolymers, namely PLA-PEAd and PLGA-PEAd at 90/10 and 75/25 w/w ratio, were prepared via reactive melt mixing, and their successful synthesis was verified by proton nuclear magnetic resonance (1H NMR and 13C NMR) and FTIR analysis. Then, the enzymic hydrolysis and cytotoxicity characteristics of them were comprehensively assessed. The results confirmed that all synthesized copolymers can be enzymatically hydrolyzed (i.e., are biodegradable) with low cytotoxicity, and hence can be used as suitable drug matrix/carriers. In the next step, the newly synthesized copolymers were used to prepare PTX-loaded NPs via o/w emulsification/solvent evaporation method. The size of the PTX-loaded NPs varied from 250 to 490 nm, depending on the polyester used, while X-ray diffraction analysis revealed that the drug was amorphously dispersed in all cases. Scanning electron microscopy showed the formation of spherical NPs with smooth surfaces, while good drug loading and encapsulation efficiency values were obtained in all cases. Finally, the in vitro dissolution analysis of all prepared PTX-loaded NPs showed biphasic drug dissolution profiles in all cases, while the use of PEAd resulted in the formation of NP having highly tunable dissolution properties.